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Human Pluripotent Stem Cell Based Developmental Toxicity Assays for Chemical Safety Screening and Systems Biology Data Generation
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In vitro models for gonadal and placental toxicity: A review and industry survey

Samuel Madureira Silva, Steven Van Cruchten, Freddy Van Goethem

    NAM Journal
    |June 29, 2026
    PubMed

    Insights

    Animal-free toxicology methods are advancing, but their use in assessing gonadal and placental toxicity is limited. Experts show optimism for future integration of these in vitro models for better human risk assessment.

    Area of Science:

    • Toxicology
    • Developmental and Reproductive Toxicology (DART)
    • In Vitro Methods

    Background:

    • A growing emphasis exists on developing animal-free testing methods in toxicology.
    • However, the integration of these methods into safety assessments, especially for gonadal and placental toxicity, remains restricted.
    • Existing animal models raise concerns regarding their predictive accuracy for human outcomes.

    Purpose of the Study:

    • To review current in vitro models for gonadal and placental biology relevant to DART.
    • To assess industry practices and expert perceptions of these in vitro methodologies.
    • To identify barriers and opportunities for adopting in vitro models in DART.

    Main Methods:

    • Literature review of in vitro models for gametogenesis, steroidogenesis, and placental function.
    • Survey of 16 DART experts on current practices and views regarding in vitro methods.
    • Analysis of survey data to understand industry reliance on animal models and acceptance of alternatives.

    Main Results:

    • Industry predominantly relies on animal models due to regulatory requirements.
    • DART experts reported limited familiarity and confidence in current in vitro models for gonadal and placental toxicity.
    • Despite current limitations, experts expressed optimism regarding the future adoption of in vitro approaches.

    Conclusions:

    • There is a significant need to increase awareness and understanding of available in vitro models for gonadal and placental toxicity.
    • Enhanced familiarity and confidence in these models are crucial for DART risk assessors.
    • Facilitating the integration of in vitro methods will lead to more reliable and human-relevant risk assessments.
    Keywords:
    Animal-free testingDevelopmental and reproductive toxicology (DART)Endocrine disruptionGametogenesisGonadal toxicityHuman-relevant modelsIn vitro toxicologyMicrofluidic systemsNew approach methodologies (NAMs)Organ-on-a-chipOrganoidsPlacental toxicityRegulatory toxicologySteroidogenesisSurvey study

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